1. Field of the Invention
This invention relates to a method of purifying .alpha.-L-aspartyl-L-phenylalanine methyl ester (hereinafter abbreviated as .alpha.-APM) from mixtures containing, as impurities, at least 3-benzyl-6-carboxymethyl-2,5-dioxopiperazine (hereinafter abbreviated as DKP) by efficiently removing the impurities after precipitation with aqueous hydrochloric acid.
2. Discussion of the Background
.alpha.-APM is a peptide sweetener having a degree of sweetness about 200 times as high as that of sucrose. It is a low-calorie substance of good quality which has been in great demand in recent years. However, the compound is unstable and cyclizes easily by heating to form DKP. Accordingly, .alpha.-APM prepared by any method unavoidably contains DKP as an impurity. Obtaining pure .alpha.-APM by efficiently removing DKP has been an eternal problem faced by producers of this substance. A variety of methods have been developed to solve this problem, but each suffers from a significant drawback. Japanese Patent Publication No. 35660/1977 discloses a resin used to purify .alpha.-APM but the method involves decomposition of .alpha.-APM during the operation, and complicated operations for eluting the product and regenerating the resin. Japanese Patent Publication No. 40071/1976 discloses a method of removing DKP by crystallizing it at a pH of 2-2.7. However, because DKP forms very fine, needle crystals, which can hardly be separated continuously on an industrial scale using commonly employed equipment, such as ordinary centrifugal separators, the method is not applicable. Therefore a filter press, which has low operation efficiency, must be used. Japanese Patent Kokai No. 117445/1974 discloses an n-butanol extraction method, therefore, the solvent n-butanol has to be recovered. In addition, any of these methods require a crystallization step to recover .alpha.-APM after the operations described above, and hence two steps are essential in order to purify .alpha.-APM by removing DKP.